This study seeks to elucidate the causes of and relationship between the failure of gluconeogenesis and mitochondrial energy-linked function in hypovolemic shock. Using a modified Wiggers' model of hemorrhagic shock, guinea pigs will be sacrificed when they have required reinfusion of 30% of their previously shed blood. Blood glucose, hepatic glycogen, ATP, ADP, lactate, inorganic phosphate, and phosphoenolypyruvate (PEP) will be determined. Hepatic mitochondrial will be isolated by differential centrifugation. Mitochondrial energy-linked functions will be determined polarographically and gluconeogenic capability will be determined by in vitro PEP synthesis. For data analysis the results will be grouped into shocked and non-shocked controls and the shocked group will be subdivided into those with coupled versus those with uncoupled oxidative phosphorylation. Differences in the correlation coefficient of hepatic glycogen content with blood glucose concentration between the coupled and uncoupled shocked animals will demonstrate the effect of uncoupled oxidative phosphorylation on in vivo gluconeogenesis. Student's t-test will be used to compare the whole hepatic tissue concentrations of ATP, ADP, lactate, inorganic phosphate, and PEP. The relationship between these in vivo indices of metabolic injury and in vitro assessment of energy-linked functions with a substrate sensitive to ischemic injury may clarify the role of mitochondrial injury in cell death. The nature of the synchrony between the in vitro dysfunction of energy-linked reactions and failure of PEP synthesis will elucidate the mechanism of gluconeogenic failure. Separation of the medium from the mitochondria following in vitro incubation and subsequent determination of pyruvate, oxaloacetate, malate, PEP, ATP, and ADP in each will elucidate the role of disordered nucleotide and carboxylic acid transport in the genesis of mitochondrial dysfunction. Identification of the primary mechanism of gluconeogenic and energy-linked dysfunction will establish a framework for therapeutic interventions to sustain both gluconeogenesis and energy-yielding reactions during circulatory failure.